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PubMed1979

Tributyltin-mediated exchange diffusion of halides in lipid bilayers.

This paper describes the effect of tributyltin (TBT) on the inorganic anion permeability of lipid bilayers. When this compound is added in micromolar concentrations to one or both sides of a phosphatidyl ethanolamine (PE) membrane formed in 0.1 M NaCl or KCl (pH 7), there is no change in the electrical conductance. Under these circumstances, the Cl self-exchange flux measured with 36Cl (MCl) increases from a value of approximately 10(-12) mol.cm-2.s-1, to approximately 10(-8) mol.cm-2.s-1. It was further found that the relation between chloride flux and [TBT] and [Cl] can be described as: MCl = B[TBT] [Cl]. When chloride was replaced by an equimolar concentration of different univalent anions in the trans compartment, the heteroexchange flux of chloride followed the sequence: I greater than Br greater than Cl greater than F greater than NO3. Under all experimental conditions tested, the chloride flux was always more than 10(3) times the maximum flux predicted from the value of the membrane conductance, and at least 100 times higher than the expected fluxes of ion pairs (TBT-Cl) diffusing across the unstirred layers. Thus, the mechanism by which tributyltin increases anion permeability in bilayers seems to be that of an obligatory exchange diffusion, with the reaction between tributyltin and the halides occurring at the membrane surface. Measurements of interfacial potentials indicate that tributyltin chloride lowers the positive intrinsic dipole potential of PE membranes by approximately 70 mV (at a TBT concentration of 30 microM) without substantial alteration of other parameters of the bilayer. The estimated adsorption coefficient of TBT-Cl was found to be 3 x 10(-4) cm.

Bromides↗
PubMed1999

The role of calcium in pre- and postmitochondrial events in tributyltin-induced T-cell apoptosis.

Using a novel dual-channel FACS methodology, the organotin compound TBT (2 microM) was shown to induce rapid (maximal by 3 min) and sustained elevations in intracellular calcium levels [Ca(2+)](i) in Jurkat T cells. This was preceded by mitochondrial hyperpolarization (maximal at 1 min), with subsequent loss of membrane potential, (Deltapsi(m)) over the next 15 min and was associated with the release of mitochondrial cytochrome c and the activation of type II caspases. The activation of the caspases was blocked by calcium chelation with EGTA and/or BAPTA. Interestingly, changes in Deltapsi(m) caused by TBT were not affected by chelation of intra- and extracellular calcium or by performing the experiments in a Ca(2+)-free medium. TBT also caused rapid elevation of [Ca(2+)](i) in cells lacking glycolytic ATP production. Despite this, the loss of Deltapsi(m) and the activation of type II caspases were delayed (maximal by 2 h) in these cells. Further, there was a failure to activate type II caspases in cells treated with TBT in a Ca(2+)-free medium, despite rapid release of mitochondrial cytochrome c. Consequently, these cells evaded the induction of apoptosis and were diverted to delayed necrotic deletion. Taken together, these data strongly suggest that the rapid rise in [Ca(2+)](i) caused by TBT in Jurkat T cells is not directly coupled to the induction of mitochondrial permeability transition, which rather results from a direct interaction of TBT with mitochondrial component(s) controlling pore transition. However, the rise in [Ca(2+)](i) is a prerequisite for postmitochondrial events involved in caspase activation prior to the induction of apoptosis.

Apoptosis↗
PubMed1983

Effects of postnatal trimethyltin or triethyltin treatment on CNS catecholamine, GABA, and acetylcholine systems in the rat.

The effects on brain neurochemistry of two neurotoxic tin compounds, trimethyltin (TMT) hydroxide and triethyltin (TET) sulfate, were examined. Long-Evans rats were treated with TMT hydroxide (1 mg/kg, i.p.) on alternate days from day 2 to 29 of life. These treatments caused a weight deficit of 10-20% by the time the animals were killed on day 55 by head-focused microwave irradiation. These TMT treatments are known to cause severe neuronal loss in the hippocampus and lesser damage in other brain regions. Accordingly, the concentration of gamma-aminobutyric acid (GABA) was decreased in the hippocampus; however, acetylcholine and choline concentrations were unaffected. These data suggest that TMT-induced effects on GABA systems are greater than that due simply to generalized neuronal loss. The TMT treatments also caused a significant decrease in dopamine concentrations in the striatum, but did not alter the concentrations of dihydroxyphenylacetic acid or homovanillic acid, the acidic metabolites of dopamine. Conversely, concentrations of dopamine and norepinephrine in the brain stem and norepinephrine in the cerebellum were not altered. Despite reports in the literature of TMT-induced neuronal damage in areas of the cortex, no effects on GABA, acetylcholine, or choline levels were found in the cortical areas examined, or in the hypothalamus. TET sulfate (0.3 mg/kg/day) was administered for 6 consecutive days of every week during days 2-29 of life. This dose is lower than that needed to cause intramyelin edema, yet it does result in long-term behavioral changes. Despite this, no changes in the concentration of any of the measured neurotransmitters or their metabolites were detected. In concert, these data demonstrate that neurochemical methods should not be used as neurological "screens," but rather to define specific mechanisms suggested by detailed behavior, pharmacological, and/or physiological studies.

Acetylcholine↗
PubMed1999

QUASIMEME laboratory performance study of the biological effects of tributyltin (imposex and intersex) on two marine gastropod molluscs.

The disruption of the endocrine systems of gastropod molluscs and consequential physiological changes (imposex and intersex) are used as biomarkers for environmental contamination by tributyltin compounds. The first international laboratory performance study on the determination of imposex and intersex in neogastropod molluscs, Nucella lapillus and Littorina littorea has been undertaken by the QUASIMEME (Quality Assurance of Information for Marine Environmental Monitoring in Europe) project. Samples of live gastropods were distributed and participants were asked to record shell height and sex, together with penis length and vas deferens sequence stage (VDS) in Nucella or the intersex stage (IS) and prostate length in Littorina. Calculations were made of vas deferens sequence index (VDSI) and the relative penis size index (RPSI) in Nucella and of intersex stage index (ISI) and the average female prostate length (FPrL) in Littorina. Thirteen (87%) of the 15 participating laboratories returned data. The remaining two laboratories asked to participate in later exercises. For Nucella, seven laboratories reported sex ratios significantly different from the reference laboratory data. Differences in penis length measurements between laboratories were largely random, although there were indications of systematic errors affecting the data from three laboratories. Seven laboratories reported satisfactory data (Z-score magnitude of Z < 2) for VDSI. The inclusion of a high proportion of sub-adults in the Nucella samples may have made separation of the sexes more difficult than in mature adults. The sub-adults will have had smaller pene than mature adults in the same population, and therefore any errors (random or systematic) in the measurement of penis length or observation of reproductive organs would have a potentially greater impact on the final reported values of the summary imposex indices. The Littorina sample did not show a high degree of intersex (ISI = 0.41). The laboratories could determine the sex of Littorina reliably and only one laboratory reported data significantly different from the reference laboratory. All except two laboratories reported satisfactory data for ISI.

Animals↗
PubMed1997

Tributyltin potentiates 3,3',4,4',5-pentachlorobiphenyl-induced cytochrome P-4501A-related activity.

Induction of cytochrome P-4501A protein and induction of related enzyme activity are hallmark physiological responses following exposure to planar halogenated aromatic hydrocarbons (HAHs) such as 3,3',4,4',5-pentachlorobiphenyl (PCB 126; PeCB). Environments contaminated by HAHs are often contaminated by mixtures of anthropogenic contaminants, including organometallic compounds. Both HAHs and organometallics easily bioconcentrate and bioaccumulate in aquatic food chains that may ultimately be linked to humans through seafood consumption. Tributyltin (TBT), a marine biocide, has been detected in many aquatic environments due to its primary use as a marine antifoulant agent. Exposure to TBT, as well as several PCBs, has been associated with immunotoxicity, neurotoxicity, and endocrine disruption. Recently TBT has been shown to inhibit cytochrome P-4501A activity in vitro, but information concerning these effects in vivo and in combination with classical inducers of P-4501A, such PeCB, is lacking. We exposed female B6C3F1 mice to 0.01, 0.1, and 1.0 mg/kg PeCB, TBT, or both in combination, with corn oil (CO) serving as a carrier control. Cytochrome P-4501A protein levels and related benzo[a]pyrene hydroxylation (BaP-OHase) activity were measured following a single acute intraperitoneal (ip) dose or seven daily injections. Body, thymus, and liver weights were used to monitor general physiological responses following exposure. P-4501A levels and BaP-OHase activity were significantly elevated in mice exposed to PeCB alone. This effect was enhanced by coexposure to low levels of TBT; PeCB-induced P-4501A-related activity was potentiated at the low range of each. The highest dose of TBT, however, inhibited these activities when given in combination with PeCB. Thymic atrophy was evident only in mice exposed daily to 0:1 and 1.0 mg/kg PeCB alone, or to a combination of the lowest and highest dose of PeCB and TBT, respectively. Because environmental levels of TBT are not expected to be as high as the highest level used in our toxicological studies, we conclude that environmental exposure to TBT may potentiate, rather than inhibit, the activity of environmental levels of HAHs that are associated with P-4501A induction.

Animals↗
PubMed1988

Early metabolic responses of retinal neurons to trimethyltin intoxication.

Chronic systemic exposure of rats to the neuronotoxic compound trimethyltin (TMT) results in increased incorporation of radioactive precursors into retinal proteins and glycoproteins. Because this increased metabolic activity is accompanied by minimal subcellular pathological alterations and almost no neuronal necrosis, we suggested that it may represent an early, reactive (compensatory) response (Brain Res. 398, 298-304; 1986). We have now investigated the development of this metabolic response to TMT in more detail. Beginning at 30 d of age, rats received weekly doses of TMT (4 mg/kg body wt) by gavage for up to 7 wk; rates of incorporation of [35S]methionine and [3H]fucose into retinal proteins and glycoproteins, respectively, were then determined using in vitro retinal incubations. The apparent rates of protein synthesis and glycoprotein glycosylation in retinas from TMT-treated animals were normal or slightly decreased after 1-3 wkly doses, but were increased after 4 doses and more markedly increased after 7 doses. Glycoprotein glycosylation was increased to a greater degree (192% of control after 7 wk of dosing) than was protein synthesis (134% of control). The increased incorporation in retinas from TMT-treated animals persisted when retinas were incubated with "flooding" concentrations of precursor (1 mM), suggesting that these increases were not owing to alterations in the size of retinal precursor pools. The preferential increase in glycoprotein glycosylation was partially owing to a selective increase in glycosylation of two molecular species with apparent mol wt of 32 and 45 KDa. Quantitative autoradiographic analysis of newly synthesized proteins and glycoproteins indicated that the TMT-induced increase in metabolic activity was not specific or selective for any retinal layer or cell type. We suggest that the preferential activation of glycoprotein glycosylation, and in particular the increased glycosylation of the 32 and 45 KDa glycoprotein species, may represent part of a compensatory metabolic response of retinal neurons to TMT-induced neuronal injury.

Animals↗
PubMed2005

Butyltin species in benthic and pelagic organisms of the Saguenay Fjord (Canada) and Imposex occurrence in common whelk (Buccinum undatum).

The distribution and accumulation of butyltins in various tissues of 13 benthic and pelagic species living in the sub-Arctic Saguenay Fjord (Canada) were investigated. Butyltin contamination was ubiquitous in this ecosystem with tributyltin (TBT) biota to sediment accumulation factors (BSAF) ranging between 0.22 and 11, but without any important biomagnification between trophic levels. The large range of butyltin compounds accumulating within different tissues of the species collected from all trophic levels was from 7 to 1238 ng Sn g(-1) d.w. and indicates an exceptional contamination level only found in northern coastal areas exposed to an intensive traffic of commercial ships. Results show that bioaccumulation in organisms depends on three main factors: (1) the actual contamination level in their habitat, (2) their assimilation pathway by water, sediment or diet, and (3) their ability to metabolize TBT and excrete metabolites. By their lack of an efficient TBT degradation system, bivalves are subject to accumulate more butyltins (from 890 to 993 ng Sn g(-1) d.w. for TBT and from n.d to 138 ng Sn g(-1) d.w. for metabolites) whereas most burrow-dwelling organisms are able to degrade TBT and their butyltin levels ranged from 86 to 239 ng Sn g(-1) d.w. for TBT and from 7 to 106 ng Sn g(-1) d.w. for metabolites. Acadian redfish (Sebastes fasciatus) feeding preferentially on shrimps and small crustaceans rich in TBT showed a contamination level about three times higher than eelpout (Licodes vahlii). The latter species living in contact with the sediment and feeding on worms and other burrowing species had a lower proportion of TBT in their tissues. Finally, deleterious effects of butyltins in the Saguenay Fjord were assessed by the significant occurrence of Imposex in common whelk (Bucinum undatum) in two sites from Baie des Ha! Ha!. Results revealed that the effects of Imposex were accentuated close to the source of contamination, at Port-Alfred harbour, since the total of imposexed whelks collected at site A (the mouth of Baie des Ha! Ha!) was 12.5% and reached 52.6% at site B (Port Alfred). Although the incidence or frequency of imposex was low in site A compared to site B, the relative penile length index (RPL) values, a measure of the degree or severity of imposex, was similar at both sites indicating the presence of TBT with higher concentrations in site B.

Animals↗
PubMed2005

Health status of Mya arenaria bivalves collected from contaminated sites in Canada (Saguenay Fjord) and Denmark (Odense Fjord) during their reproductive period.

The purpose of this study was to examine the health status and gametogenetic activity in Mya arenaria clams collected at various sites in the St. Lawrence Estuary (Quebec, Canada) and in the Odense Fjord (Denmark). Clam soft tissues were analyzed for metals/metalloids and organotin compounds to confirm their exposure to these contaminants. Their health status was assessed by a test battery of biomarkers designed to measure the early biological effects of contaminants, which include expression of defence mechanisms such as xenobiotic conjugation (glutathione S-transferase), expression of stress proteins (i.e., heme oxygenase and metallothioneins), changes in gametogenetic activity, and individual morphometric characteristics. Clam tissues were also examined for the presence of oxidative damage to lipids, formation of DNA strand breaks, and alterations in heme metabolism. The results showed that clams sampled from sites with either ferry activity or intensive boat traffic in marinas were contaminated by metals/metalloids such as Ag, Al, As, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sn, V, and Zn. The clams also contained relatively high amounts of tributyltin (TBT) in their tissues (in the ng TBT/g range for both areas), with digestive glands containing more organotins than did gonadal tissues. Moreover, clams collected from TBT-contaminated sites had higher amounts of tin-heme adducts and lower total heme in their digestive glands. Condition factor, age distribution, and sex ratio were significantly altered in clams from impacted sites in the Saguenay Fjord and accompanied by an increased male/female sex ratio. Gametogenetic activity was also negatively affected, as revealed by reductions in gonadosomatic index, maturation index, aspartate transcarbamylase activity, and vitellogenin-like proteins. The Saguenay Fjord clams displayed a complex pattern of stress responses and damage such as increased heme oxygenase activity, phase 2 conjugation enzyme activity, lipid peroxidation, and altered DNA strand breaks. The integration of biomarker response data into a biomarker index at the whole-individual level (morphometric characteristics) and for various organs (gill, digestive gland, and gonad) revealed that, relative to the control site, morphological characteristics and gonadal activity were most affected at the most contaminated site, while the effects were more pronounced in the digestive gland and gill at moderately impacted sites. We conclude that the health status of M. arenaria clams at these contaminated sites is compromised, with obvious disruption of reproductive activity.

Animals↗
PubMed2006

Subacute administration of tributyltin chloride modulates neurotransmitters and their metabolites in discrete brain regions of maternal mice and their F1 offspring.

Tributyltin (TBT) compounds have been used as anti-fouling agents and the central nervous system is one of its target organs. TBT-induced modulations of neurotransmitters in the brains of adult mice have been reported. However, little is known about the developmental neurotoxicity of TBT. In this study, we evaluated the effects of TBT on neurotransmitters and their metabolites in discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at one, two and three weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed in the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control. TBT may induce a decrease in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring may be due to several factors such as age, dose, route, sex and pregnancy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Effects of in utero tributyltin chloride exposure in the rat on pregnancy outcome.

Tributyltin, an organotin, is ubiquitous in the environment. The consumption of contaminated marine species leads to human dietary exposure to this compound. Tributyltin is an endocrine disruptor in many wildlife species and inhibits aromatase in mammalian placental and granulosa-like tumor cell lines. We investigated the effects of tributyltin chloride exposure on pregnancy outcome in the Sprague-Dawley rat. Timed pregnant rats were gavaged either with vehicle (olive oil) or tributyltin chloride (0.25, 2.5, 10, or 20 mg/kg) from days 0-19 or 8-19 of gestation. On gestational day 20, dams were sacrificed, and pregnancy outcome was determined. Tributyltin and its metabolites (dibutyltin, monobutyltin) were measured in maternal blood by gas chromatography. Both tributyltin and dibutyltin were present in maternal blood at approximately equal concentrations, whereas monobutyltin contributed minimally to total organotins. Organotin concentrations increased in a dose-dependent pattern in dams, independent of the window of exposure. Tributyltin chloride administration significantly reduced maternal weight gain only at the highest dose (20 mg/kg); a significant increase in post-implantation loss and decreased litter sizes, in addition to decreased fetal weights, was observed in this group. Tributyltin chloride exposure did not result in external malformations, nor was there a change in sex ratios. However, exposure to 0.25, 2.5, or 10 mg/kg tributyltin chloride from gestation days (GD) 0-19 resulted in a significant increase in normalized anogenital distances in male fetuses; exposure from days 8-19 had no effect. There was a dramatic increase in the incidence of low weight (< or =0.75 of the mean) fetuses after exposure to 20 mg/kg tributyltin chloride. Delayed ossification of the fetal skeleton was observed after in utero exposure to either 10 mg/kg or 20 mg/kg tributyltin chloride. Serum thyroxine and triiodothyronine levels were reduced significantly in dams exposed to 10 and 20 mg/kg tributyltin chloride throughout gestation; in dams treated with tributyltin from GD 8-19, serum thyroxine concentrations, but not triiodothyronine, were significantly decreased at both the 2.5 and 10 mg/kg exposures. Thus, maternal thyroid hormone homeostasis may be important in mediating the developmental toxicity of organotins.

Administration, Oral↗
PubMed1976

Triethyltin sulfate-induced neuropathy in rats. Electrophysiologic, morphologic, and biochemical studies.

Adult rats given high orally administered doses of triethyltin (TET) sulfate lost weight, developed hind limb wasting, and became paraplegic or quadriplegic within three weeks of intoxication. A 33% reduction in the motor nerve conduction velocity (MNCV) of the sciatic nerve in the absence of significant demyelination was observed. There was observed, however, intramyelinic edema formation and an increased number of axonal neurofilaments and neurotubules; changes that paralleled the decrease in MNCV during the period of intoxication. Although the animals became asymptomatic and the MNCV normalized within two to three weeks of discontinuing the TET intoxication, the intramyelinic vacuoles and the increased numbers of neurofilaments and neurotubules persisted.

Animals↗
PubMedDate not supplied

Tripropyltin(iv) complexes with some selected bioligands in 50% v/v dioxane/water mixture.

The interaction of the tri-n-propyltin(IV) (TPT) with some selected bioligands having a variety of model functional groups were investigated using potentiometric technique at 25 degrees C and 0.1 M ionic strength in 50% v/v dioxane/water mixture. TPT is hydrolyzed to give [(C3H7)3SnOH], [(C3H7)3Sn(OH)2]-, and [((C3H7)3Sn)2OH]+. Amino acids and DNA constituents form 1:1 and 1:2 complexes. Peptides form 1:1 complexes and the corresponding deprotonated amide species. The protonated complexes are formed with amino acids, peptides and some DNA constituents. The hydrolysis constants and the stepwise formation constants of the complexes formed in solution were calculated using the nonlinear least-square program MINIQUAD-75. The participation of different ligand functional groups in binding to organotin is discussed. The speciation diagrams of the various complex species were evaluated as a function of pH.

Amino Acids↗
PubMed2006

Study of neonatal exposure to androgenic endocrine disruptors, testosterone and dihydrotestosterone by normal-phase HPLC.

Neonatal exposure to androgen induces developmental abnormalities in the male reproductive system. To investigate whether neonatal exposure affects spermatogenesis in juvenile and pubertal testis, Sprague-Dawley rat pups were given androgen or various androgenic endocrine disruptors by a single injection on the day of birth at concentrations ranging between 4 mm to 200 mm, and sacrificed on day 21 (juvenile) or 50 (puberty). The testes were weighed and examined histologically at each stage. Further, the metabolites of steroidogenesis were analyzed using normal-phase high-performance liquid chromatography. Neonatal exposure significantly reduced testis weights and steroidogenesis of juveniles. Neonatal exposure to testosterone and dihydrotestosterone still suppressed pubertal steroidogenesis, although testis weight was completely restored during puberty.

Androgens↗
PubMed1988

A selective ion monitoring assay for tributyltin and its degradation products.

Tributyltin (TBT) is a biocide which has been shown to enter the aquatic environment by release from antifouling paints. TBT is acutely toxic to some marine organisms at concentrations near 1 microgram l-1 and physiological changes may occur at low nanogram per liter concentrations. Gas chromatography/mass spectrometry (GC/MS) (methane chemical ionization) has been used for identification (full scanning) and quantification (selected ion monitoring) of TBT, dibutyltin (DBT) and monobutyltin (MBT). The butyltins were extracted from environmental water samples with hexane/0.2% tropolone and derivatized with hexyl magnesium bromide to form hexylbutyltins. Selected ion monitoring was at m/z 319 (TBT) and m/z 347 (DBT, MBT and tripentyltin, the internal standard). Calibration curves prepared in natural water were linear and detection limits were less than 2 ng l-1. GC/MS and GC with flame photometric detection were compared as quantification methods for environmental samples and were shown to give similar results at the low nanogram per liter levels.

Gas Chromatography-Mass Spectrometry↗
PubMed1985

Effect of tricyclohexylhydroxytin on synaptosomal Ca2+-dependent ATP hydrolysis and rat brain subcellular calmodulin.

Effect of tricyclohexylhydroxytin (plictran) on Ca2+-ATPase activity was studied in rat brain synaptosomes under in vitro and in vivo conditions. Plictran inhibited basal Ca2+-ATPase activity with an IC50 value of 6 nM suggesting its interaction with calcium transport phenomenon. Plictran inhibited calmodulin (CaM) activated Ca2+-ATPase in a concentration-dependent manner. A complete reversal of calmodulin activation of Ca2+-ATPase was observed with 2-3 nM plictran. A 50 per cent decrease of CaM activated Ca2+-ATPase was observed with 0.5 nM plictran, a concentration at which no significant effect was observed on basal enzyme activity. Of all the brain fractions studied, calmodulin levels in P2 fractions alone were reduced significantly to about 75 per cent of control values in plictran treated rats. The synaptosomal Ca2+-ATPase was also decreased by 35 per cent, 42 per cent and 65 per cent in 10, 20 and 40 mg plictran kg-1 day-1 treated rats for 3 days respectively. The activity levels of Ca2+-ATPase in 10 and 20 mg plictran kg-1 day-1 treated rats were restored to normal level by exogenously added calmodulin. These results suggest that plictran may disrupt synaptic function by altering calcium and calmodulin regulated processes in the central nervous system.

Animals↗
PubMed1987

Inhibition of beta-adrenergic stimulated calcium pump of rat cardiac sarcoplasmic reticulum by tricyclohexyltin hydroxide.

The effects of tricyclohexyltin hydroxide (Plictran), an organotin acaricide, on 45Ca2+ uptake and Ca2+ ATPase were studied in vitro and in vivo in rat heart ventricular membrane vesicles, primarily sarcoplasmic reticulum. There was a concentration dependent inhibition of both 45Ca2+ uptake and Ca2+ ATPase in vivo as well as in vitro. Isoproterenol, a beta-adrenergic agonist, stimulated 45Ca2+ uptake and Ca2+ ATPase of sarcoplasmic reticulum and this was also inhibited by Plictran. Since cardiac relaxation is mediated by beta-adrenergic stimulation via Ca+ uptake by sarcoplasmic reticulum, the inhibition of calcium pump activity by Plictran may result in alterations in cardiac Ca2+ fluxes leading to cardiac dysfunction.

Animals↗
PubMed2005

Kinetic properties of turkey pancreatic lipase: a comparative study with emulsified tributyrin and monomolecular dicaprin.

Using the classical emulsified system and the monomolecular film technique, we compared several interfacial properties of turkey pancreatic lipase (TPL) and human pancreatic lipase (HPL). TPL, like HPL, presented the interfacial activation phenomenon when vinyl ester was used as substrate. In the absence of colipase and bile salts, using tributyrin emulsion or monomolecular films of dicaprin at low surface pressure, TPL, unlike HPL, hydrolyzes pure tributyrin emulsion as well as dicaprin films maintained at low surface pressures. TPL was also able to hydrolyze triolein emulsion in the absence of any additive and despite the accumulation of long-chain free fatty acids at the interface. The difference of behaviors between TPL and HPL can be explained by the penetration power of each enzyme. The enzyme that presents the maximal pi(c) (TPL) interacts more efficiently with interfaces, and it is not denaturated at high interfacial energy. Turkey pancreatic lipase is more active on rac-dicaprin than HPL; a maximal ratio of 9 was found between the catalytic activities of the two lipases measured at their surface pressure optima (20 mN m(-1)). A kinetic study on the surface pressure dependency, stereospecificity, and regioselectivity of TPL was performed using enantiopure diglyceride (1,2-sn-dicaprin and 2,3-sn-dicaprin) and a prochiral isomer (1,3-dicaprin) that were spread as monomolecular films at the air-water interface. At low surface pressure (15 mN m(-1)), TPL acts preferentially on primary carboxylic ester groups of the diglyceride isomers (1,3-dicaprin), but at high surface pressure (23 mN m(-1)), this enzyme prefers both adjacent ester groups of the diglyceride isomers (1,2-sn-dicaprin and 2,3-sn-dicaprin). HPL prefers adjacent ester groups of the diglyceride isomers (1,2-sn-dicaprin and 2,3-sn-dicaprin). Furthermore, TPL was found to be markedly stereospecific for the sn-1 position of the 1,2-sn-enantiomer of dicaprin at low surface pressure (15 mN m(-1)), while at high surface pressure (23 mN m(-1)), this lipase presents a stereopreference for the sn-3 position of the 2,3-sn-enantiomer of dicaprin. HPL is stereospecific for the sn-1 position of the 1,2-sn-enantiomer of dicaprin both at 15 and 23 mN m(-1).

Animals↗
PubMed2004

Environmental pollutant tributyltin promotes Th2 polarization and exacerbates airway inflammation.

It has been shown that a relatively high dose of tributyltin (TBT), which is recognized as a particularly notable environmental pollutant, exerts immunotoxic effects such as thymic atrophy via induction of T cell apoptosis. However, the effect of low doses of TBT on the immune responses remains unknown. Here we show that environmentally relevant doses of TBT promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4(+) T cells primed with anti-CD3 and splenic antigen-presenting cells (APC). TBT-induced Th2 polarization was indirect, working through APC via suppression of IL-12 production by macrophages/DC and the augmentation of IL-10 production by B cells. Th2 polarization was also induced in mice treated with TBT and immunized with OVA or infected with Nippostrongylus brasiliensis. Furthermore, airway inflammation in mice sensitized and challenged with OVA was exacerbated by the administration of TBT with concomitant augmentation of Th2-type immunity. Our results highlight the fact that an important environmental pollutant TBT may present significant risk for the induction of allergic diseases via promotion of Th2 polarization.

Animals↗